Cerebral perfusion augmentation

ABSTRACT

Methods are provided for partial aortic occlusion for cerebral perfusion augmentation in patients suffering from global or focal cerebral ischemia. The descending aorta is accessed. A device is then located downstream from the takeoff of the brachiocephalic artery. The device is operated to at least partially obstruct blood flow in the aorta during systole and diastole. A physiologic parameter can be measured. The device can then be adjusted to modify the degree of obstruction based on the measured physiologic parameter.

This is a continuation of U.S. application Ser. No. 10/411,743, filedApr. 11, 2003, which is a continuation of U.S. application Ser. No.09/531,443, filed Mar. 20, 2000, now U.S. Pat. No. 6,635,046, which is adivisional of U.S. application Ser. No. 09/260,371, filed Mar. 1, 1999,now U.S. Pat. No. 6,231,551. All of the above patents and applicationsare incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates generally to medical devices. Moreparticularly, the invention relates to methods and devices foraugmenting blood flow to a patient's vasculature. More particularly, theinvention relates to apparatus and methods which provide partialobstruction (“coarctation”) to aortic blood flow to augment cerebralperfusion in patients with global or focal ischemia. The devices andmethods also provide mechanisms for continuous constriction and variableblood flow through the aorta.

BACKGROUND OF THE INVENTION

Patients experiencing cerebral ischemia often suffer from disabilitiesranging from transient neurological deficit to irreversible damage(stroke) or death. Cerebral ischemia, i.e., reduction or cessation ofblood flow to the central nervous system, can be characterized as eitherglobal or focal. Global cerebral ischemia refers to reduction of bloodflow within the cerebral vasculature resulting from systemic circulatoryfailure caused by, e.g., shock, cardiac failure, or cardiac arrest.Shock is the state in which failure of the circulatory system tomaintain adequate cellular perfusion results in reduction of oxygen andnutrients to tissues. Within minutes of circulatory failure, tissuesbecome ischemic, particularly in the heart and brain.

The most common form of shock is cardiogenic shock, which results fromsevere depression of cardiac performance. The most frequent cause ofcardiogenic shock is myocardial infarction with loss of substantialmuscle mass. Pump failure can also result from acute myocarditis or fromdepression of myocardial contractility following cardiac arrest orprolonged cardiopulmonary bypass. Mechanical abnormalities, such assevere valvular stenosis, massive aortic or mitral regurgitation,acutely acquired ventricular septal defects, can also cause cardiogenicshock by reducing cardiac output. Additional causes of cardiogenic shockinclude cardiac arrhythmia, such as ventricular fibrillation.

Treatment of global cerebral ischemia involves treating the source ofthe systemic circulatory failure and ensuring adequate perfusion to thecentral nervous system. For example, treatment of cardiogenic shock dueto prolonged cardiopulmonary bypass consists of cardiovascular supportwith the combination of inotropic agents such as dopamine, dobutamine,or amrinone and intra-aortic balloon counterpulsation. Vasoconstrictors,such as norepinephrine, are also administered systemically to maintainsystolic blood pressure (at approximately above 80 mmHg). Unfortunately,these agents produce a pressure at the expense of flow, particularlyblood flow to small vessels such as the renal arteries. The use of thevasoconstrictors is, therefore, associated with significant sideeffects, such as acute renal failure.

Focal cerebral ischemia refers to cessation or reduction of blood flowwithin the cerebral vasculature resulting from a partial or completeocclusion in the intracranial or extracranial cerebral arteries. Suchocclusion typically results in stroke, a syndrome characterized by theacute onset of a neurological deficit that persists for at least 24hours, reflecting focal involvement of the central nervous system and isthe result of a disturbance of the cerebral circulation. Other causes offocal cerebral ischemia include vasospasm due to subarachnoid hemorrhageor iatrogenic intervention.

Traditionally, emergent management of acute ischemic stroke consists ofmainly general supportive care, e.g. hydration, monitoring neurologicalstatus, blood pressure control, and/or anti-platelet or anti-coagulationtherapy. Heparin has been administered to stroke patients with limitedand inconsistent effectiveness. In some circumstances, the ischemiaresolves itself over a period of time due to the fact that some thrombiget absorbed into the circulation, or fragment and travel distally overa period of a few days. In June 1996, the Food and Drug Administrationapproved the use of tissue plasminogen activator (t-PA) or Activase®,for treating acute stroke. However, treatment with systemic t-PA isassociated with increased risk of intracerebral hemorrhage and otherhemorrhagic complications. Aside from the administration of thrombolyticagents and heparin, there are no therapeutic options currently on themarket for patients suffering from occlusion focal cerebral ischemia.Vasospasm may be partially responsive to vasodilating agents. The newlydeveloping field of neurovascular surgery, which involves placingminimally invasive devices within the carotid arteries to physicallyremove the offending lesion may provide a therapeutic option for thesepatients in the future, although this kind of manipulation may lead tovasospasm itself.

In both global and focal ischemia, patients develop neurologic deficitsdue to the reduction in cerebral blood flow. Treatments should includemeasures to increase blood flow to the cerebral vasculature to maintainviability of neural tissue, thereby increasing the length of timeavailable for interventional treatment and minimizing neurologic deficitwhile waiting for resolution of the ischemia. Augmenting blood flow tothe cerebral vasculature is not only useful in treating cerebralischemia, but may also be useful during interventional procedures, suchas carotid angioplasty, stenting or endarterectomy, which mightotherwise result in focal cerebral ischemia, and also cardiac procedureswhich may result in global cerebral ischemia, such as cardiaccatheterization, electrophysiologic studies, and angioplasty.

New devices and methods are thus needed for augmentation of cerebralblood flow in treating patients with either global or focal ischemiacaused by reduced perfusion, thereby minimizing neurologic deficits.

SUMMARY OF THE INVENTION

The invention provides vascular constriction devices and methods foraugmenting blood flow to a patient's cerebral vasculature, including thecarotid and vertebral arteries. The devices constructed according to thepresent invention comprise a constricting mechanism distally mounted ona catheter for delivery to a vessel, such as the aorta. The constrictoris collapsed to facilitate insertion into and removal from the vessel,and expanded during use to restrict blood flow. When expanded, theconstrictor has a maximum periphery that conforms to the inner wall ofthe vessel, thereby providing a sealed contact between it and the vesselwall. The constrictor typically has a blood conduit allowing blood flowfrom a location upstream to a location downstream. The devices furtherinclude a variable flow mechanism in operative association with theblood conduit, thereby allowing blood flow through the conduit to beadjusted and controlled. The devices can optionally include a manometerand/or pressure limiter to provide feedback to the variable flowmechanism for precise control of the upstream and downstream bloodpressure. Other medical devices, such as an infusion, atherectomy,angioplasty, hypothermia catheters or devices (selective cerebralhypothermia with or without systemic hypothermia, and typicallyhypothermia will be combined with measures to increase perfusion toovercome the decreased cerebral blood flow caused by the hypothermia,such that hypothermia and coarctation are complimentary), orelectrophysiologic study (EPS) catheter, can be introduced through theconstrictor to insert in the vessel to provide therapeutic interventionsat any site rostrally.

In a preferred embodiment, the expandable constrictor comprises an outerconical shell and an inner conical shell. Each shell has an apex and anopen base to receive blood flow. One or a plurality of ports traversesthe walls of the two conical shells. Blood flows through the open baseand through the ports. The inner shell can be rotated relative to theouter shell so that the ports align or misalign with the ports in theouter shell to allow variable blood flow past the occluder, therebyproviding adjustable and controlled flow. The inner shell is rotated bya rotating mechanism, e.g., a torque cable disposed within the elongatetube and coupled to the inner shell. The constrictor can be expanded by,e.g., a resilient pre-shaped ring, graduated rings, or a beveled lipformed at the base of the shell, and collapsed by, e.g., pull wiresdistally affixed to the occluder or a guide sheath.

In another embodiment, the outer conical shell includes a plurality ofresilient flaps, which are pivotally affixed to the base or the apex andcan be displaced to variably control blood flow through the conduit. Theflaps can be displaced by a plurality of pull wires affixed to theflaps.

In still another embodiment, the constrictor comprises a firstcylindrical balloon mounted to a distal end of the catheter, and asecond toroidal balloon disposed about the cylindrical balloon. Thechamber of the first balloon communicates with an inflation lumen. Bloodflow occurs through the cylindrical balloon and through the center ofthe toroidal balloon. The toroidal balloon is expanded by inflationthrough a second and independent inflation lumen to reduce blood flowthrough the cylindrical balloon. In this manner, the first balloonprovides an inflatable sleeve and the second toroidal balloon providesvariable control of blood flow through the sleeve. Other embodimentsinclude an expandable sleeve (not a balloon) surrounded by a toroidalballoon for adjustably constricting the flow of blood through thecylindrical sleeve.

In a preferred method, the occlusion devices described above areinserted into the descending aorta through an incision on a peripheralartery, such as the femoral, subclavian, axillary or radial artery, in apatient suffering from global or focal cerebral ischemia, during cardiacsurgery (including any operation on the heart, with or without CPB), orduring aortic surgery (during circulatory arrest, as for aortic archsurgery, repair of an abdominal aortic aneurysm, or thoracic aneurysmrepair, to reduce perfusion and the amount of blood loss in theoperating field). The devices can be introduced over a guide wire. Withassistance of transesophageal echocardiography (TEE), transthoracicechocardiography (TTE), intravascular ultrasound (IVUS), aortic archcutaneous ultrasound, or angiogram, the constrictor is positioneddownstream from the takeoff of the brachiocephalic artery and upstreamfrom the renal arteries. The constrictor is expanded to partiallyocclude blood flow in the aorta and maintained during systole, duringdiastole, or during systole and diastole. The constrictor preferablyachieves continuous apposition to the wall of the vessel, resulting infewer emboli dislodgment. The pressure limiter, connected to the rotaryunit and the pressure monitor, prevents the upstream and downstreamblood pressure from exceeding, respectively, a set maximum and minimumpressure differential.

Flow rates can be varied within one cardiac cycle (e.g., 80% duringsystole, 20% during diastole, or 70% during systole, 30% duringdiastole), and every few cycles or seconds (e.g., 80% for 6 cycles, 20%for 2 cycles, or 70% for 5 cycles, 10% for 1 cycle). In certain cases itmay be preferred to cycle to cycle between lesser and greater occlusionso that the brain does not autoregulate. This ensures constant andcontinued increased cerebral perfusion. In this manner, blood in thedescending aorta is diverted to the cerebral vasculature, therebyincreasing cerebral perfusion and minimizing neurological deficits. Byselectively increasing cerebral blood flow, the use of systemicallyadministered vasoconstrictors or inotropic agents to treat shock may bereduced or eliminated.

In another method, in patients anticipating a major cardiothoracicsurgery, such as abdominal aortic aneurysm repair, the device isintroduced and deployed approximately 24 hours prior to surgery, therebyinducing mild artificial spinal ischemia. This induces endogenousneuroprotective agents to be released by the spinal cord and/or brain inresponse to the ischemia, thereby protecting the tissue from ischemicinsult of surgery. This technique is known as “conditioning”. Thedevices are inserted into the descending aorta. To induce spinalischemia, the constrictor is positioned downstream from the takeoff ofthe brachiocephalic artery and upstream from the renal artery andexpanded to partially occlude blood flow in the aorta, resulting inreduction of blood flow to the spinal cord. A similar technique may beemployed to condition the brain to stimulate production ofneuroprotective agents. To induce cerebral ischemia, the constrictor ispositioned upstream from the takeoff of the innominate artery, orbetween the innominate artery and the left common carotid artery.

Prolonged hypertension often causes ischemic damage to the kidneys. Instill another method, the partial occlusion devices are introducedperipherally and positioned in the renal arteries to reduce bloodpressure to the renal vasculature, thereby minimizing damage to thekidneys that might otherwise result from hypertension.

It will be understood that there are many advantages in using thepartial aortic occlusion devices and methods disclosed herein. Forexample, the devices can be used (1) to provide variable partialocclusion of a vessel; (2) to augment and maintain cerebral perfusion inpatients suffering from global or focal ischemia; (3) to condition thebrain or spinal cord to secrete neuroprotective agents prior to a majorsurgery which will necessitate reduced cerebral or spinal perfusion; (4)to prolong the therapeutic window in global or focal ischemia; (5) toaccommodate other medical devices, such as an atherectomy catheter; (6)prophylactically by an interventional radiologist, neuroradiologist, orcardiologist in an angiogram or fluoroscopy suite; (7) for prevention ofcerebral ischemia in patients undergoing procedures, such as coronarycatheterization or surgery, where cardiac output might fall as a resultof arrhythmia, myocardial infarction or failure; (8) to treat shock,thereby eliminating or reducing the use of systemic vasoconstrictors;and (8) to prevent renal damage in hypertensives.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a patient's systemic arterial circulation relevant tothe present invention.

FIG. 2 illustrates an embodiment of the devices constructed according tothe present invention for providing partial occlusion of a vessel.

FIG. 3 illustrates a constrictor of the device depicted in FIG. 2.

FIG. 4A illustrates an outer conical shell employed in the constrictorof FIG. 3.

FIG. 4B illustrates an inner conical shell employed in the constrictorof FIG. 3.

FIG. 5 illustrates an alternative embodiment of the constrictors of FIG.3 having elongate rectangular ports.

FIG. 6 illustrates another embodiment of the occluder having a beveledlip.

FIG. 7 illustrates another embodiment of the occluder having a pluralityof graduated rings.

FIG. 8 illustrates complete misalignment of the ports on the outer andinner conical shells.

FIG. 9 illustrates partial alignment of the ports on the outer and innerconical shells.

FIG. 10 illustrates complete alignment of the ports on the outer andinner conical shells.

FIG. 11 illustrates another embodiment of the device for providingpartial occlusion of a vessel.

FIG. 12 illustrates another embodiment of the constrictor employed inthe device of FIG. 11.

FIG. 13A illustrates a frontal view of the constrictor of FIG. 12 havinga plurality of preformed flaps extending perpendicular to thelongitudinal axis of the constrictor.

FIG. 13B illustrates a frontal view of the flaps of FIG. 13A under anexternal force.

FIG. 13C illustrates a frontal view of the constrictor of FIG. 12 havinga plurality of preformed flaps extending parallel to the longitudinalaxis of the constrictor.

FIG. 13D illustrates a frontal view of the flaps of FIG. 13C under anexternal force.

FIG. 14 illustrates another embodiment of the occluder having flapsincluded in the collar of the outer conical shell.

FIG. 15 illustrates still another embodiment of the device for providingpartial occlusion of a vessel.

FIG. 16 illustrates an embodiment of the constrictor employed in thedevice of FIG. 15.

FIG. 17 illustrates the constrictor of FIG. 16, having an inflatedring-shaped balloon for reducing blood flow through a blood conduit.

FIG. 18 illustrates the occluder of FIG. 16, having a deflatedring-shaped balloon.

FIG. 19 illustrates a suction/atherectomy catheter introduced throughthe constrictor of FIG. 16.

FIG. 20 illustrates a perfusion and an EPS catheter introduced throughthe constrictor of FIG. 16.

FIG. 21A illustrates the constrictor of FIG. 3 inserted in the aortadownstream from the left subclavian artery and partially occludingaortic blood flow.

FIG. 21B illustrates the constrictor of FIG. 14 inserted in the aortadownstream from the left subclavian artery and partially occludingaortic blood flow.

FIG. 22 illustrates the constrictor of FIG. 3 inserted in the aortadownstream from the right brachiocephalic artery and partially occludingaortic blood flow.

FIG. 23 illustrates a suction/atherectomy catheter introduced throughthe constrictor of FIG. 3 and inserted in the left carotid arteryproximal to a thromboembolic occlusion.

FIG. 24 illustrates the constrictor of FIG. 3 inserted in the aortaupstream from the lumbar or lumbar or spinal arteries.

FIG. 25 illustrates the constrictor of FIG. 3 inserted in the renalarteries.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The devices and methods disclosed herein are most useful in treatingpatients suffering from global cerebral ischemia due to systemiccirculatory failure, and focal cerebral ischemia due to thromboembolicocclusion of the cerebral vasculature. However, it will be understoodthat the devices and methods can be used in other medical conditions,such as hypertension and spinal cord conditioning.

Systemic arterial circulation relevant to the methods of the presentinvention is described in FIG. 1. During systole, oxygenated bloodleaving heart 8 enters aorta 10, which includes ascending aorta 12,aortic arch 14, and descending aorta 22. The aortic arch gives rise tobrachiocephalic trunk 16, left common carotid artery 18, and leftsubclavian artery 20. The brachiocephalic trunk branches into rightcommon carotid artery 24 and right subclavian artery 26. The right andleft subclavian arteries, respectively, give rise to right vertebralartery 28 and left vertebral artery 34. The descending aorta gives riseto a multitude of arteries, including lumbar (i.e., spinal) arteries 38,which perfuse the spinal cord, renal arteries 40, which perfuse thekidneys, and femoral arteries 42, which perfuse the lower extremities.

FIG. 2 depicts occlusion catheter 100 for use in the methods describedherein. The device includes elongate catheter 102, distally mountedexpandable constrictor, i.e., occluder, 104 having distal opening 124and variable flow mechanism 108. The constrictor, when expanded, hasmaximum periphery 110, which conforms to the inner wall of a vessel toform a secure seal with the vascular wall, such that blood flow throughthe vessel can be effectively controlled. Opening 124 receives bloodfrom distal the constrictor and controls the passage of blood proximalthe constrictor. Variable flow mechanism 108, connected to rotary unit150, operates the constrictor, thereby controlling (1) the flow ratethrough the occlusion, and (2) upstream blood pressure. Preferably, thedevice includes manometer 112, which is connected to pressure monitor156 and pressure limiter 114. Rotary unit 150 receives blood pressuremeasurements from the manometer. Pressure limiter 114, connected to therotary unit and the pressure monitor, prevents the upstream anddownstream blood pressure from exceeding, respectively, a set maximumand minimum pressure differential. A proximal end of the catheter isequipped with adapter 103, from which pull wires 132 can be manipulatedfor collapsing the occluder and to which the rotary unit, pressuremonitor, and/or pressure limiter can be connected.

Referring to FIG. 3, the occlusion device comprises catheter 102 andconstrictor 104. The catheter is constructed from a biocompatible andflexible material, e.g., polyurethane, polyvinyl chloride, polyethylene,nylon, etc. The catheter includes lumen 116 through which variousoperative elements pass. Alternatively, the catheter may include morethan one lumen to support various operative elements. The catheter alsoincludes proximal adapter 103 (see FIG. 2), which provides an interfacebetween the catheter and the various instruments received by thecatheter. The occluding mechanism consists of outer conical shell 118and inner conical shell 136, each having a distal open base and aproximal apex. Pre-shaped ring 130 is affixed to base 120 of the outershell to facilitate expansion of the constrictor. The ring is formed ofa resilient material, capable of expanding the occluder to achieve amaximum periphery, which is defined by the outer circumference of thering. Ring 130, may, in certain embodiments, further include ananchoring mechanism, such as hooks, bonded to the outer circumference ofthe ring. Expansion of the ring causes the grasping structure to engagethe surface of the vessel wall, thereby securing the occluder andpreventing displacement in the vessel due to force exerted by bloodflow. In other embodiments, the anchoring is provided by an adhesivestrip, vacuum, or merely by frictional engagement of the vessel lumen bythe ring.

The constrictor can be collapsed to facilitate insertion into andremoval from a vessel. A plurality of pull wires 132 (FIG. 2) aredisposed within torque cable 148, and are distally connected to base 120of outer shell 118 and proximally passes through adapter 103. Theconstrictor is collapsed by applying a tensile force on wires 132, usingtorque cable 148 to provide leverage to the pull wires, thereby drawingthe circumference of the open base 120 towards its center and collapsingthe occluder. A guide sheath (not shown) can be alternatively used tocollapse the constrictor. Using this technique, the guide sheath wouldcover the constrictor and be withdrawn to release the constrictor andadvanced to collapse the constrictor.

Opening 124 is formed in base 138 and 120 of the respective inner andouter conical shells to provide an inlet for blood flow. Conicalinterior 106 communicates with ports 128 of the outer shell. When theconstrictor is deployed, blood flows into opening 124, through interior106, and exits through ports 128. The occluding mechanism comprisesinner conical shell 136 (partially shown in phantom in FIG. 3), which isrotatably disposed within outer shell 118 as shown in FIGS. 8, 9, and10. The inner shell can be rotated relative to the outer shell throughtorque cable 148, which is disposed in lumen 116 of catheter 102.

Manometer 112 comprises upstream pressure tube 152 and downstreampressure tube 154, both connected proximally to a pressure monitor toprovide respective blood pressure measurements upstream and downstreamthe constrictor. The upstream pressure tube extends distal to opening124, or may be attached to the inner shell. The downstream pressure tubeextends through an orifice in the catheter proximal to the constrictor.The upstream and downstream blood pressure measurements are recorded anddisplayed by the pressure monitor at a proximal end of the catheter. Apressure limiter, programmed with a maximum pressure threshold to limitthe upstream blood pressure and a minimum pressure threshold to limitthe downstream blood pressure, is connected to the pressure monitor toreceive pressure measurements therefrom, and transmits information to arotary unit. The limiter thereby prevents the rotary unit from rotatingthe inner shell relative to the outer shell in a manner that would causethe upstream blood pressure to exceed the maximum threshold, or thedownstream blood pressure to fall below the minimum threshold. Withoutthe rotary unit, torque cable 148 can also be manually rotated to obtaindesired upstream and downstream blood pressures. An audible alarm may beincorporated into the pressure limiter to sound when blood pressuresexceeds the thresholds. The pressure limiter may further comprise aninterlocking device. The interlocking device, in operative associationwith upstream and downstream tubes 152 and 154, can lock inner shell 136with respect to outer shell 118 as blood pressures approach the setthresholds. It should be noted that although the rotary unit, pressuremonitor, and pressure limiter are shown as separate units, they may beincorporated into an integral unit.

Referring to FIGS. 4A and 4B, the expanded constrictor comprises outerconical shell 118 having base 120 and apex 122, and inner conical shell136 having base 138 and apex 140. The constrictor is preferably composedof a biocompatible material coated with heparin to prevent bloodclotting. The conical shape of the expanded constrictor minimizesturbulence caused by placement of the occluder in the vessel. The outerand inner shells include 2, 3, 4, 5, 6, or any other number of ports 128and 144, respectively, in communication with the conical interior topermit blood flow through the occluder. The inner shell can be rotatedrelative to the outer shell, so that ports 144 communicate with ports128. Apices 122 and 140 of the respective outer and inner shells furthercomprise collar 126 and 142. The collars may include engaging threads,so that collar 142 can be inserted and secured into collar 126, andbonded to a distal end of the torque cable, such that the inner shell iscoupled to and rotates with the torque cable. A rotary unit, preferablyincluding a stepper motor (not shown), may be mechanically coupled to aproximal end of the torque cable to provide precise rotational positionof the inner shell relative to the outer shell, thereby providingvariable flow through the occluder.

Instead of having the circular ports in the inner and outer shells asdepicted in FIGS. 4A and 4B, the constrictor may include 2, 3, 4, 5, 6,or any other number of ports having other suitable geometric shapes.FIG. 5 depicts constrictor 104 having a plurality of ports constructedas elongate rectangular slots 175.

FIG. 6 depicts another embodiment of the constrictor, which comprisesbeveled lip 140 having distal end 142 and proximal end 141. The proximalend is affixed to base 120 of the outer conical shell. The proximal endhas a larger diameter than the distal end and is everted to prevent theconstrictor from being displaced in the direction of blood flow, therebysecuring the constrictor in the vessel.

Still another embodiment of the occluder may includes 1, 2, 3, 4, 5, orany other number of graduated inflatable rings. In FIG. 7, ring 151 isaffixed to the base of the conical shell. Ring 153, having the smallestinflated diameter, is attached to ring 152, which is then attached toring 151, having the largest inflatable diameter. The fully inflatedrings will have a thickness of approximately 2 to 3 millimeters. Similarto the beveled lip of FIG. 8, the rings prevent the outer conical shellfrom being displaced in the direction of blood flow, thereby securingthe constrictor in the vessel.

The flow rate of blood through the constrictor can be easily controlledby rotating inner conical shell 136 (shown with dotted lines) relativeto outer conical shell 118 as depicted in FIGS. 8, 9, and 10. In FIG. 8,the inner shell is rotated so that ports 144 and 128 are completelymisaligned, thereby achieving no flow through the ports and completevascular occlusion distally. As the inner shell is rotated clockwiserelative to the second shell in FIG. 9, ports 144 on the inner shellbecome partially aligned with ports 128 on the outer shell, therebyachieving partial flow through the ports and partial vascular occlusion.In FIG. 10, with continuing clockwise rotation of the inner shell, ports144 become completely aligned with ports 128, thereby achieving maximumflow through the ports. To provide a broader and more predictable rangeof blood flow through the conduit, the ports of the inner and outershells are preferably of equal size and number such that they may alignwith each other.

FIG. 11 depicts another embodiment of the occlusion device for partialocclusion of blood flow in a vessel. Device 200 comprises elongatecatheter 202, distally mounted expandable constrictor 204 with maximumperiphery 210, opening 224, and variable flow mechanism 208 operativelyassociated with the constrictor. The catheter includes adapter 203 atits proximal end. Preferably, the device includes manometer 212 andpressure limiter 214, and pressure monitor 240. The pressure monitorrecords and displays blood pressure data received from the manometer.Longitudinal positioning unit 208, receiving signals from pressurelimiter 214, and controls variable flow mechanism 208 to providevariable blood flow through the constrictor.

Referring to FIG. 12, catheter 202 includes lumen 216. Constrictor 204comprises hollow conical shell 218 having base 220 and apex 222. Theinner circumference of the base forms opening 224, which provides adistal inlet for blood flow through the constrictor. The innercircumference of apex 222 forms collar 228 with proximal opening 226,which provide an outlet for blood flow through the constrictor. Theconical interior, disposed within shell 218, communicates with opening224 distally and opening 226 proximally. When the base of theconstrictor is positioned upstream in a vessel, blood flows into opening224, through the conical interior, and exits downstream through opening226. The catheter is bonded to collar 228 about a portion of its innercircumference. The constrictor is expanded by operation of ring 230, abeveled lip, or a series of graduated toroidal balloons as describedabove. The constrictor is collapsed and may be delivered to a vessellocation by using a guide sheath.

The manometer comprises upstream pressure tube 236 and downstreampressure tube 238, which are disposed in lumen 216 of the catheter andconnected proximally to a pressure monitor. The upstream pressure tubeextends distal from the constrictor or may be bonded to the innersurface of the conical shell, thereby providing upstream blood pressuremeasurement. The downstream pressure tube extends through an orifice inthe catheter proximal to the constrictor, thereby providing downstreamblood pressure measurement.

The variable flow mechanism comprises a plurality of flaps 230 pivotallyaffixed to base 220. The flaps are preferably made of a resilientmaterial, such as Nitinol, to resist movement caused by blood flowthrough the conduit. A plurality of pull wires 232, disposed throughlumen 216, are distally connected to flaps 230, such that applying atensile force to the wires pivotally displaces flaps 230 from theirpreformed position. Three of the flaps (shown in dotted lines) aredisplaced inward. Releasing the wires allows the resilient flaps torelax and return to their preformed position. The pull wires are coupledproximally to the longitudinal positioning unit, which provides precisedisplacement of the flaps relative to opening 224. Alternatively, wires232 can be manually tensed to operate the flaps. The pressure limiterreceives pressure measurements from the pressure monitor and transmitssignals to the longitudinal positioning unit to prevent the upstream anddownstream blood pressures from exceeding the set thresholds.

FIGS. 13A, 13B, 13C, and 13D depict frontal views of the constrictorhaving flaps in various positions for controlling blood flow. In FIG.13A, preformed flaps 230 extend radially inward toward the longitudinalaxis of the catheter, as in the absence of a displacing force, i.e., anexternal force other than that created by blood flow. When theconstrictor is positioned in the descending aorta, for example, the sizeof opening 224 and blood flow through the opening is minimized, therebyproviding maximal aortic occlusion. In the presence of a displacingforce, such as pulling the wires to displace flaps 230 from theirpreformed position as depicted in FIG. 13B, the size of aperture 224 andblood flow through the conduit increases, thereby providing partialaortic occlusion.

Alternatively, preformed flaps 230 extend parallel to the longitudinalaxis of opening 224 in the absence of a displacing force as depicted inFIG. 13C. The size of opening 224 and blood flow through the conduit aremaximized, thereby providing minimal blood flow occlusion. In thepresence of a displacing force, flaps 230 are pivotally displaced fromtheir preformed position as depicted in FIG. 13D. The size of opening224 and blood flow through the opening are minimized, thereby providingmaximal blood flow occlusion. Thus, by pivotally displacing flaps 230relative to opening 224, the size of the opening and flow rate throughthe constrictor is controlled to provide variable vessel occlusion.

The constrictor shown in FIG. 12 can be alternatively mounted oncatheter 202, such that base 220 is proximal to apex 222 as shown inFIG. 14A. In this embodiment, flaps 230 are formed on open apex 222.When constrictor 204 is inserted downstream in the aorta, for example,pressure tube 238 extends distally from opening 226 to providedownstream blood pressure measurements, whereas pressure tube 236extends proximally through an orifice in the catheter to provideupstream blood pressure measurements.

In FIG. 15, another embodiment of the device comprises catheter 302, adistally mounted occluder 304 with maximum periphery 310, blood passage306 disposed within the constrictor, and variable flow mechanism 308 inoperative association with the blood conduit. Inflation device 334communicates with the constrictor, and inflation device 338 communicateswith the variable flow mechanism. The device preferably includesproximal adapter 303, manometer 312, and pressure limiter 314. Pressuremonitor 312 records and displays blood pressure data from the manometer.The pressure limiter is connected to the pressure monitor and to aninterlocking valve on inflation device 338, such that the blood pressureupstream and downstream the constrictor can be controlled to preventfrom exceeding set thresholds.

Referring to FIG. 16, constrictor 304 is mounted to a distal end ofcatheter 302 having lumen 316. The constrictor comprises a sleeve orcylindrical balloon 318 having outer wall 320 and inner wall 322, whichenclose chamber 323. The cylindrical balloon has first end 324 withopening 328 and second end 326 with opening 330. Catheter 302 is bondedto inner wall 322 of the cylindrical balloon. Inflation tube 332, housedwithin lumen 316 of the catheter, communicates distally with thecylindrical balloon and proximally with a syringe or other inflationdevice. The cylindrical balloon can be expanded or collapsed byinjecting or removing air, saline, or other medium. Occlusion isprovided by toroidal balloon 334 disposed about the outer or innersurface of sleeve 318 and communicating with inflation tube 336 and asyringe. The inflation device may include an interlocking valve toprevent unintended deflation.

Lumen 306 communicates with opening 328 distally and opening 328proximally. When deployed in a vessel, blood flows through lumen 306 andexits downstream opening 330. The constrictor may further include ananchoring structure, shown in FIG. 16 as rings 333, which are disposedabout outer wall 320 of the cylindrical sleeve and define maximumperiphery 310 of the occluder.

Manometer 312 comprises upstream pressure tube 340 and downstreampressure tube 342, which are operatively connected proximally to apressure monitor. Pressure tube 340 is bonded to the lumen of thecylindrical balloon and extends distal to provide upstream bloodpressure measurements, while tube 342 emerges from the catheter proximalthe occluder to provide downstream blood pressure measurements.

In FIG. 17, fluid is injected to expand balloon 334, therebyconstricting sleeve 318. As a result, blood flow is constricted. In FIG.18, balloon deflation allows sleeve 318 to revert back to its pre-shapedgeometry, increasing blood flow therethrough. Thus, balloon 334 can beinflated and deflated to vary the cross-sectional diameter of lumen 306to vary flow rate.

The occlusion devices described herein can be employed with a variety oftherapeutic catheters to treat vascular abnormalities. For example, asdepicted in FIG. 19, suction/atherectomy catheter 402 can be insertedthrough lumen 306, such that the suction/atherectomy catheter isindependently movable relative to occlusive device 300. Catheter 402includes elongate tube 404 and distally located aspiration port 406,cutting device 408, and balloon 410 for removing thromboembolic materialin a vessel.

In FIG. 20, infusion catheter 502 and EPS catheter 504 are insertedthrough opening 206 of occlusion device 200, such that catheter 502 and504 are independently movable relative to occlusion device 200. Theinfusion catheter, which includes elongate tube 506, distally locatedperfusion port 508, and expandable balloon 510, can be used to removethromboembolic material in a vessel. EPS catheter 504, which includeselongate tube 512 and distally located ablation device 514, may be usedto map out or ablate an extra conduction pathway in the myocardialtissue, e.g., in patients suffering from Wolff-Parkinson-White syndrome.The occlusion device, capable of augmenting cerebral perfusion, istherefore useful not only in facilitating definitive treatment but alsoin cerebral ischemia prevention during EPS and other cardiacinterventions or cardiac surgery, such as coronary catheterization,where sudden fall in cerebral blood flow may occur due to arrhythmia,myocardial infarction, or congestive heart failure.

Referring to FIG. 21A, occlusion device 100 described above can be usedto partially occlude blood flow in aorta 10 of a patient suffering fromglobal cerebral ischemia due to, e.g., septic shock, congestive heartfailure, or cardiac arrest. Constrictor 104 can be introduced in itscollapsed geometry through an incision on a peripheral artery, such asthe femoral, subclavian, axillary, or radial artery, into the patient'saorta. A guide wire may first be introduced over a needle, and thecollapsed constrictor is then passed over the guide wire and the needleto position distal to the takeoff of left subclavian artery 20 in thedescending aorta. The constrictor is expanded, such that maximumperiphery 110 of the occluder, formed by expandable ring 130, sealinglycontacts the inner aortic wall. The position and orientation of thecollapsed or expanded device can be checked by TEE, TTE, aortic archcutaneous ultrasound in the emergency room, or IVUS and angiography inthe angiogram suite.

The expanded constrictor is maintained during systole, during diastole,or during systole and diastole, during which blood distal to thebrachiocephalic artery is forced to pass through opening 106, therebyproviding a continuous partial occlusion of aortic blood flow.Alternatively, partial occlusion of aortic blood flow can beintermittent. As a result, blood flow to the descending aorta ispartially diverted to brachiocephalic artery 16, left subclavian artery20, and left carotid artery 18, thereby augmenting blood flow to thecerebral vasculature. In treating global ischemia, such as in shock,cerebral perfusion is increased by increasing blood flow through bothcarotid and vertebral arteries. Additionally, blood flow to the aorta ispartially diverted to the coronary arteries by using the occlusiondevice, thereby augmenting flow to the coronary arteries. Using thepartial occlusion methods during systemic circulatory failure may,therefore, improve cardiac performance and organ perfusion. Byselectively increasing cerebral and coronary blood flow in this manner,the dosage of commonly used systemic vasoconstrictors, such as dopamineand norepinephrine, may be reduced or eliminated.

Alternatively, the device of FIG. 14, much like the device used toextinguish the flame of a candle, can be introduced through an incisionon left subclavian artery 36 as depicted in FIG. 21B. Constrictor 204 isinserted in aorta 22 distal to the takeoff of the left subclavian arteryto provide partial, variable, and/or continuous aortic occlusion and isadvanced antegrade into the descending aorta. This device isparticularly useful in situations where peripheral incision can not bemade on the femoral arteries due to arteriosclerosis, thrombosis,aneurysm, or stenosis.

The devices and methods described in FIGS. 21A and 21B are useful intreating stroke patients within few minutes of stroke symptom, and thetreatment can be continued up to 96 hours or more. For example, intreating focal ischemia due to a thromboembolic occlusion in the rightinternal carotid artery the constrictor may be position distal to thetakeoff of the left subclavian. As a result, blood flow is diverted tobrachiocephalic artery 16 and left CCA to augment both ipsilateral andcontralateral collateral circulation by reversing direction of flowacross the Circle of Willis, i.e., increasing flow in the right externalcarotid artery and left common carotid artery. The collateral cerebralcirculation is further described in details in co-pending U.S.application Ser. No. ______ [Lyon & Lyon Docket No. 239/096],incorporated herein by reference.

In treating focal ischemia due to a thromboembolic occlusion in the leftinternal carotid artery, for example, the constrictor can be positionedproximal to the takeoff of left carotid artery 18 and distal to thetakeoff of brachiocephalic artery 16 as shown in FIG. 22. Contralateralcollateral enhancement is provided by increasing flow through thebrachiocephalic artery, thereby reversing blood flow in the rightposterior communicating artery, right PCA, left posterior communicatingartery 68 and anterior communicating artery, resulting in increasedperfusion to the ischemic area distal to the occlusion and minimizingneurological deficits. Alternatively, the constrictor may be positioneddistal to the takeoff of the left subclavian artery to provide bothipsilateral and contralateral collateral augmentation. Ipsilateralcirculation is enhanced by increasing flow through the left externalcarotid artery and reversing flow along the left ophthalmic artery, bothof which contribute to increased flow in the left ICA distal to theocclusion.

As a result of partially occluding aortic blood flow, blood pressuredistal to the aortic occlusion may decrease, and this may result in areduction in renal output. Blood pressure proximal the aortic occlusionwill increase and may result in excessive rostral hypertension. Theblood pressures, measured by the manometer, are monitored continuously,and based on this information the occlusion is adjusted to avoidperipheral organ damage. After resolution of the cerebral ischemia, theconstrictor is collapsed and removed, thereby removing the aorticocclusion and restoring normal blood flow in the aorta.

In FIG. 23, constrictor 304 is inserted in aorta 10 and can be used toremove thromboembolic material 72 from left common carotid artery 18,while augmenting and maintaining cerebral perfusion distal to theoccluding lesion. The occluder may be introduced through a guide sheathuntil it is positioned distal to left subclavian artery 20. In emergencysituations, the constrictor can be inserted through a femoral incisionin the emergency room, and atherectomy/suction catheter 402 can beinserted through the constrictor under angioscopic vision in theangiogram suite after the patient is stabilized hemodynamically. Theatherectomy/suction catheter, which includes expandable balloon 410,distal aspiration port 406, and atherectomy device 408, is introducedthrough opening 306 until its distal end is positioned in left commoncarotid artery 18 proximal to the thromboembolic occlusion.

Constrictor 304 is then expanded to partially occlude aortic blood flow,thereby increasing perfusion to the ischemic region distal to theoccluding lesion by enhancing ipsilateral collateral flow through leftexternal carotid artery 46 and left vertebral artery 34 andcontralateral collateral flow to right carotid artery 24 and rightvertebral artery 28. The variable flow mechanism of constrictor 304 canbe adjusted to control blood flow to the cerebral vasculature and theblood pressure. Balloon 410 of catheter 402 is expanded in the leftcommon carotid artery, thereby creating a closed chamber betweenconstrictor 410 and the thromboembolic occlusion. Suction can be appliedto aspiration port 406 to create a negative pressure in the closedchamber, thereby increasing the pressure differential across thethromboembolic occlusion, which may dislodge the occluding lesion ontothe aspiration port and remove the occluding lesion. Thromboembolicmaterial 72 may be further removed by atherectomy device 408. Themethods herein can also be used to remove thromboembolic occlusion inthe vertebral artery. The occlusion device 304, therefore, not onlyaugments cerebral perfusion in patients suffering from focal stroke orglobal ischemia, but also maintains cerebral perfusion while waiting forinvasive or noninvasive intervention. The devices and methods of usingatherectomy/suction catheter 102 are further described in copending U.S.application Ser. No. ______ [Lyon & Lyon Docket No. 239/096],incorporated herein by reference.

During abdominal aortic aneurysm (AAA) surgery, lumbar or spinalarteries, which provide blood supply to the spinal cord, are oftendissected away from the diseased abdominal aorta, resulting in reductionof blood flow to the spinal cord. The devices herein disclosed may beused to condition the spinal cord prior to AAA repair, thereby reducingthe damage resulting from spinal ischemia during surgery. In FIG. 24,constrictor 104 is inserted in aorta 10 and expanded preferably distalto left subclavian artery 20 and proximal to lumbar arteries 38. As aresult, blood flow to the lumbar or spinal arteries is reduced. Whenthis device is used in patients anticipating a major thoracoabdominalsurgery, such as AAA repair, approximately 24 hours prior to surgery,blood flow to the lumbar arteries can be intentionally reduced to inducemild spinal ischemia, thereby conditioning the spinal cord to produceneuroprotective agents which may protect the spinal cord from moresignificant ischemic insult during surgery.

In hypertension, end organ damage often results, e.g., cardiac, renal,and cerebral ischemia and infarction. The devices and methods herein maybe employed in hypertension to protect the kidneys from ischemic insult.In FIG. 25, constrictors 104, which can be introduced through a femoralartery, are inserted in right renal artery 80 and left renal artery 82.The constrictors are expanded to partially occlude blood flow fromdescending aorta 10 to the renal arteries, thereby reducing bloodpressure distal to the occlusion. The constrictors can be deployed forthe duration of any systemic hypertensive condition, thereby protectingthe kidneys from damage that might otherwise be caused by thehypertension.

The length of the catheter will generally be between 20 to 150centimeters, preferably approximately between 30 and 100 centimeters.The inner diameter of the catheter will generally be between 0.2 and 0.6centimeters, preferably approximately 0.4 centimeters. The diameter ofthe base of the outer conical shell will generally be between 0.3 and3.0 centimeters, preferably approximately 0.5 and 2.0 centimeters. Thediameter of the inflated balloon occluder will generally be between 0.3and 3.0 centimeters, preferably approximately 0.5 and 2.0 centimeters.The ports of the inner and outer conical shells will generally have adiameter of between 1 to 6 millimeters, preferably approximately 3 to 4millimeters. The foregoing ranges are set forth solely for the purposeof illustrating typical device dimensions. The actual dimensions of adevice constructed according to the principles of the present inventionmay obviously vary outside of the listed ranges without departing fromthose basic principles.

Although the foregoing invention has, for the purposes of clarity andunderstanding, been described in some detail by way of illustration andexample, it will be obvious that certain changes and modifications maybe practiced which will still fall within the scope of the appendedclaims.

1-20. (canceled)
 21. A method for increasing cerebral blood flow,comprising the steps of: advancing a catheter into the descending aorta,the catheter having a proximal region, a distal region, and anexpandable member mounted on the distal region; locating the expandablemember in the abdominal aorta; expanding the expandable member topartially obstruct blood flow in the aorta during systole and diastole;measuring a physiologic parameter; and adjusting the expansion of theexpandable member based on the measured physiologic parameter.
 22. Themethod of claim 21, wherein the physiologic parameter is blood pressure.23. The method of claim 21, wherein the physiologic parameter iscerebral blood flow.
 24. The method of claim 21, wherein the expandablemember is a balloon.
 25. The method of claim 21, wherein blood flow tothe cerebral vasculature increases by at least 20%.
 26. A method forincreasing cerebral blood flow, comprising the steps of: advancing acatheter into the descending aorta, the catheter having a proximalregion, a distal region, and an expandable member mounted on the distalregion; locating the expandable member in the abdominal or thoracicaorta; expanding the expandable member to partially obstruct blood flowin the aorta during systole and diastole; measuring a physiologicparameter; and adjusting the expansion of the expandable member based onthe measured physiologic parameter.
 27. The method of claim 26, whereinthe physiologic parameter is blood pressure.
 28. The method of claim 26,wherein the physiologic parameter is cerebral blood flow.
 29. The methodof claim 26, wherein the expandable member is a balloon.
 30. The methodof claim 26, wherein blood flow to the cerebral vasculature increases byat least 20%.
 31. A method for increasing cerebral blood flow,comprising the steps of: advancing a catheter into the descending aorta,the catheter having a proximal region, a distal region, and anexpandable member mounted on the distal region; locating the expandablemember in the aorta inferior to the heart; expanding the expandablemember to partially obstruct blood flow in the aorta during systole anddiastole; measuring a physiologic parameter; and adjusting the expansionof the expandable member based on the measured physiologic parameter.32. The method of claim 31, wherein the physiologic parameter is bloodpressure.
 33. The method of claim 31, wherein the physiologic parameteris cerebral blood flow.
 34. The method of claim 31, wherein theexpandable member is a balloon.
 35. The method of claim 31, whereinblood flow to the cerebral vasculature increases by at least 20%.
 36. Amethod for increasing cerebral blood flow, comprising the steps of:advancing a catheter into the descending aorta, the catheter having aproximal region, a distal region, and an expandable member mounted onthe distal region; locating the expandable member in the descendingaorta; expanding the expandable member to partially obstruct blood flowin the aorta during systole and diastole for a sustained period withoutoccluding the aorta; measuring a physiologic parameter; and adjustingthe expansion of the expandable member based on the measured physiologicparameter.
 37. The method of claim 36, wherein the physiologic parameteris blood pressure.
 38. The method of claim 36, wherein the physiologicparameter is cerebral blood flow.
 39. The method of claim 36, whereinthe expandable member is a balloon.
 40. The method of claim 36, whereinblood flow to the cerebral vasculature increases by at least 20%.